在KRAS,NRAS和BRAF的特定位点突变与结肠直肠癌中ctDNA的频率相关
Fumihiro Yoshimura1, Yoichiro Yoshida1,2, Teppei Yamada1
1Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
Cancer reports (Hoboken, N.J.)
|July 23, 2025
概括
在循环瘤DNA (ctDNA) 中的突变等位基因频率 (MAF) 根据结直肠癌 (CRC) 的特定基因突变部位而异. 为了准确地预测转移风险,为每个突变部位建立不同的MAF切线值至关重要.
科学领域:
- 在瘤学瘤学.
- 分子诊断学 分子诊断学
- 遗传学 是一个遗传学.
背景情况:
- 在结直肠癌 (CRC) 切除后早期预测转移风险对于治疗优化至关重要.
- 循环瘤DNA (ctDNA) 是一个关键的生物标志物,但其实用性受到突变等位基因频率 (MAF) 未定义的切断值的限制.
- 目前的MAF评估使用了对基因的统一切断值,无论特定的突变部位如何.
研究的目的:
- 研究MAF与CRC中的特定遗传突变部位之间的关系.
- 确定突变部位是否影响ctDNA复发预测值.
- 为了确定基因突变地点是否影响ctDNAMAF值.
主要方法:
- 使用数字PCR对102名CRC患者具有KRAS,NRAS和BRAF突变的ctDNA进行分析.
- 在手术前,手术后1日,7日和30日检查MAF.
- 在同一基因内的不同突变位点中对MAF值进行比较.
主要成果:
- 在所有评估时间 (p < 0.001) 中,在突变的编码位之间观察到MAF的显著差异.
- 与其他KRAS位点 (代码12,13) 和BRAF代码600相比,KRAS代码146始终显示出更高的MAF值.
- 此外,BRAF编码子600的MAF也比KRAS编码子12高.
结论:
- MAF值受到特定突变部位的显著影响,即使是在同一基因内.
- 这些发现表明需要在CRC中进行ctDNA分析的突变部位特定的MAF切割值.
- 将MAF切线量身定制到个别突变部位可能会提高转移风险预测的准确性.
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